John Libbey Eurotext

Bulletin du Cancer

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pRB, p53, p16 INK4a, senescence and malignant transformation Volume 91, issue 5, Mai 2004

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Laboratoire d’Oncologie moléculaire, Pôle Biologie Santé, 40, avenue du Recteur‐Pineau, 86021 Poitiers

Recent works aimed at clarifying the respective roles of p16 INKa and p14 ARF (both located on the same INK4a locus on chromosome 9p21 in man) in malignant transformation come to the conclusion that p16 INK4a is the true tumor suppressor gene in man. In mouse, it is the p19 ARF knockout that suppresses the barrier protecting cells from malignant transformation. This situation is in agreement with p19 ARF‐ and p16‐mediated senescence induced by oncogenic mutated ras (Ras*) in mouse and man respectively. Other results have shown that senescence in human diploid fibroblasts is associated with heterochromatin occurrence that maintains in repressed state E2F1‐induced gens required for G 1 to S phases transition. Since RB protein is responsible for this chromatin modification, cells with any impaired RB pathway cannot enter into senescence.